Thursday, September 26, 2019

Autophagy in cancer( colonic adenoma and adenocarcinoma) Literature review

Autophagy in cancer( colonic adenoma and adenocarcinoma) - Literature review Example From this point, it is evident that the microvasculature of the tumor tissue is actually structurally and functionally deficient and hence is unable to provide blood supply that is prerequisite for appropriate tissue growth. To support this fact, there is evidence that some tumors, like the pancreas cancers are actually hypovascular (Sato et al, 2007). These conditions contribute to hyponutrient state of the tumor. However, for hypoproliferation, excess nutrient supply is mandatory and hence tumor cells are likely to use alternative source of energy and nutrients or some alternative metabolic process for the purpose. One such metabolic process is autophagy. There is evidence that some cancers, like the colon cancer, are resistant to nutrition depletion state and continue to thrive because of this metabolic process (Sato et al, 2007). Autophagy is a catabolic process that is conserved in which the organelles of the cells are self-digested. The first step in autophagy is development of isolation membrane, a lipid bilayer structure. This membrane sequesters various materials of the cytoplasm like the organelles to form autophagosomes. This step involves activation of LC3, a mammalian homologue of yeast ATG8 through an ubiquitination-like reaction that is regulated by ATG3 and 7. During activation, the proform of LC3 is cleaved into LC3-I which is soluble unlike the proform. This is then further modified into LC3-II which is membrane-bound form. This form is finally recruited by the autophagosomes which engulf the organelles (Rosenfeldt and Ryan, 2009). The engulfed organelles further fuse with the lysosomes and then mature into autolysosomes. This step also causes autodigestion and diminision of LC3 and also various other components of autophagosome. Thus autophagy has an important role to play in the provision of nutrition to cells during shortage of external supply of nutrition. Following autodigestion, aminoacids are released from the organelles and they are th e alternative sources of energy to the proliferative and nutrient deficient cells. Though, theoretically, this explanation seems logical with reference to nutrition supply to cancer cells in unfavorable environment, several controversial arguments have arisen in this regard. Some researchers are of the opinion that autophagic machinery may not be activated in cancer tissue contexts (Sato et al, 2007). However, there is enough evidence to point the role of autophagy in the pathogenesis of colon cancers. In this literature review the role of autophagy in the proliferation and thriving of colon cancers will be discussed through suitable literature review. Pathogenesis of colon cancer Cancer of the colon (and rectum) is the third most common cancer in men and women. It has been estimated that 940,000 new cases of colorectal cancer and nearly 500,000 deaths are occur worldwide each year (El- Deiry, 2006). The frequency is same both in men and women. The risk of the disease increases afte r 40 years of age (El- Deiry, 2006). Colon cancer (colorectal cancer) is almost always adenocarcinoma. The most common predisposing condition leading to adenocarcinoma is adenomatous polyps. Alterations in the adenomatous polyposis or APC gene as a result of mutations is the beginning point of development of the cancer. This gene is mutated in individuals affected by familial

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